The use of ion selective electrodes (ISEs) to determine the presence and quantity of various analytes in biological samples has become a useful diagnostic technique. Indeed, ISEs have been used to detect analytes such as magnesium, sodium, potassium, calcium, and chloride, among others. Some of these ISEs are often housed within clinical diagnostic instruments for simultaneous analysis of a large number of analytes.
Surfactants are often included in reagents used during the operation of ISEs. Various surfactants may be used for this purpose; however, the utility of the surfactant is highly dependent upon the sensing membrane of the ISE. For example, an unsuitable surfactant can result in a shift in electromotive force (EMF) bias that does not allow the electrode to measure a biologically relevant amount of an analyte.
It has been known that the concentration of lipophilic borate salt present in a sensing membrane plays an important role in a potentiometric selective electrode, especially for a magnesium ion (Mg2+) selective electrode. The level of borate present in the sensing membrane modulates the selectivity coefficient of Mg2+ over interfering cations such as Ca2+, Na+, and K+, based on cation charge number, complex stoichiometry with the neutral ionophore, and response kinetics. For the Mg2+ ISE, a borate-to-ionophore mol ratio of 155 mol % has been regarded as the optimized formulation that provides the best selectivity pattern.
As for the responding mechanism of the Mg-ISE, there are at least four competitive interactions that have been identified that interfere with the Mg2+ and ionophore (ETH5506) primary interaction at the membrane-sample interface for blood Mg2+ ISE's. These four competitive interactions are outlined below, and the causes of the interactions, as well as the various prior art attempts to overcome them, are discussed in detail herein below.    Primary mechanism (PM): ETH5506 (memb)+Mg2+ (aq)    Competitive mechanism-1 (CM-1): ETH5506 (memb)+Ca2+ (aq)    Competitive mechanism-2 (CM-2): Ion-exchange by lipophilic borate            (memb, interface)            Competitive mechanism-3 (CM-3): Ion-exchange by adsorbed blood protein layer            (interface)            Competitive mechanism-4 (CM-4): Ion-exchange by surfactant adsorption layer            (interface)        
PM and CM-1: Among these mechanisms, the primary mechanism (PM) can be differentiated from the competitive mechanism CM-1 by adjusting the borate:ionophore ratio. Stoichiometry of the Mg2+-ETH5506 ISE is 1:1 and that for Ca2+-ETH5506 ISE is 1:2. The lipophilic borate anion sites in the PVC membrane help stabilize the Mg2+-ETH5506 ISE and Ca2+-ETH5506 ISE to different extents with an electrical balance across the membrane-sample phase boundary (charge-transfer process). An optimal borate:ETH5506 mol ratio of 150 mol % has been calculated and experimentally verified (O'Donnell et al., Anal. Chim. Acta (1993) 281:129), at which the Mg-ISE gains the lowest log KpotMg,Ca (−2) with workable selectivities against Na+ and K+ (log KpotMg,Na (−4) and log KpotMg,K (−3)).
PM and CM-2: When the borate:ETH5506 mol ratio is reduced, the Mg-ISE favors to respond to Ca2+. At a borate:ETH5506 ratio of 50 mol %, the Mg-ISE tends to have equal sensitivity to Ca2+ and Mg2+ because of the different stoichiometries of Mg2+ and Ca2+ with ETH5506. When more borate is added (to a ratio of >150 mol %), the second competitive mechanism (CM-2) is seen, where the Mg-ISE tends to become an ion-exchange membrane dominated by the lipophilic borate in the membrane. The membrane's response follows Hofmeister's series. Monovalent cations are favored more than divalent cations. In addition, more Na+ and K+ interference can be expected.
PM and CM-3: Many studies have shown that blood samples tend to coagulate and aggregate on the surface of the PVC membrane, forming thin coating layers of platelet, fibrinogen, IgG, and albumin (Espadas-Torre et al., Anal. Chem. (1995) 7:3108-3114; Lim et al., Pure Appl. Chem. (2004) 76:753-764; and Surface Engineering of Blood Contacting Polymeric Biomaterials, p. 231). In the competitive mechanism CM-3, the ion-exchange properties of such a layer compete with the primary interaction (PM). This blood coating layer is sensitive to the pH (Scharbert, et al., Crit. Care (2011) 15:446) and surfactant levels of the various reagents (calibrators, wash, and QCs) utilized with the ISE. Variation of the pH may change the layer formation, and thus the ion-exchange mechanism can be affected. To prevent the competitive mechanism CM-3 from occurring on the Mg-ISE membrane, several approaches have been investigated, including using alternative polymeric materials, anti-protein adsorption coating layers, LbL, etc.
PM and CM-4: In automatic blood analyzers, surfactants are present in calibrating, rinse, and quality control solutions. Many studies have demonstrated the impact of surfactant on potentiometric sensors, especially on neutral ionophore-based Mg2+ selective electrodes (Malinowska et al., Anal. Chim. Acta (1999) 382:265-275). Surfactants containing poly(ethylene oxide) derivatives, which are widely used in automatic clinical analyzers, have shown severe impact on response performance of Mg2+ selective electrodes, including effects to response kinetics, slope, and selectivity. The mechanism of such interference is explained by the partitioning of nonionic surfactant into the membrane phase and the concomitant enhanced extraction of cations present in the sample phase. The partitioning process of the surfactant can significantly change the selectivity pattern and response kinetics of the membrane, which can be a function of the partitioning coefficients of the surfactant into the polymer membrane, the relative binding coefficients of primary and interfering ions with the surfactant and the ionophore, respectively, and/or the concentration of the surfactant that is present in the sequence of sample/calibrating/rinse solutions in the sensing system of the automatic analyzers. Moreover, the extent of the effect of the surfactant depends on the ratio of the stability constants of complexes formed with interfering cations by the surfactant and ionophore, respectively. The stronger the complexation of interfering cation with the surfactant, and the weaker the interaction of the primary ion with the ionophore within the membrane, a greater change in the potentiometric ion selectivity can be expected. However, the impact of the surfactant can be significantly reduced by using different kinds of surfactant with low HLB (hydrophile-lipophile balance), such as MEGA-8 and MEGA-9 surfactants.
Lipophilic borate has been known to interact with poly(ethylene oxide)-containing surfactants to form a complex. In neutral ionophore-based cation selective electrodes, the presence of lipophilic borate in the polymer membrane can enhance partitioning of surfactant and change the response performance of ISEs.
Therefore, new and improved magnesium sensing membrane compositions for potentiometric ion selective electrodes that overcome the disadvantages of the prior art are desired. It is to such membranes, as well as compositions, kits, devices, and methods related thereto, that the presently disclosed and claimed inventive concept(s) is directed.